Tretinoin Loaded Nanoemulsion for Acne Vulgaris: Fabrication, Physicochemical and Clinical Efficacy Assessments.

BACKGROUND AND AIM: Acne vulgaris is a common inflammatory skin condition which is treated using Tretinoin (TRE), a widely used retinoid. Nano emulations (NEs) are colloidal nano-sized particles that enhance the therapeutic efficacy of TRE and minimize adverse effects. This study is aimed at developing a TRE-loaded NE (NE-TRE) and at assessing the therapeutic effects of the formulation in acne vulgaris lesions, compared to conventional 0.05% TRE emulsion. METHOD: The high energy emulsification method was used to make NE-TRE. After obtaining stable NE, particle characterization and physicochemical properties were evaluated under accelerated conditions. Conducting a clinical study, we compared the therapeutic effects of NE-TRE and 0.05% TRE emulsion by comparing the number of acne lesions and porphyrin production in both sides of the face. RESULTS AND CONCLUSION: We successfully developed stable nanoparticles. It was a stable oil-in-water emulsion with particle size of about 150 nm, and containing circular and separated particles. In a pilot clinical study, the number of acne lesions as well as the size and intensity of porphyrin production significantly reduced after topical application of NE-TRE. This formula shows proper efficiency and good loading capacity of TRE in the drug delivery system.

Frequency and Risk Factors of Penicillin and Amoxicillin Allergy in Suspected Patients with Drug Allergy.

BACKGROUND: Unconfirmed beta-lactam allergy is a significant public health problem because of the limitations it imposes in drug selection. In this study, we aimed to evaluate patients referred for beta-lactam allergy to determine the frequency of confirmed beta-lactam allergy and identify some risk factors. METHODS: In a prospective cohort study, all referred patients to Immunology, Asthma and Allergy Research Institute in Tehran University of Medical Sciences (between 2007 - 2009) who suspected to have beta-lactam allergy were entered into this study based on having the inclusion criteria. Follow-up was performed 6 - 8 years after the final diagnosis. Diagnosis of beta-lactam allergy relies on thorough history and specific IgE measurements (ImmunoCAP), skin prick testing (SPT), intradermal testing (IDT), patch testing, and oral drug challenge test. RESULTS: Fifty-one patients with mean age of 24.5 (±18.5) years were enrolled in this study. Based on workups, beta-lactam allergy was confirmed in 16 (31.4%) patients, suspicious in 22 (43.1%) patients and ruled out in 13 (25.5%) patients.  During the follow-up, 3 patients with suspicious drug allergy consumed the culprit drug with no reaction so allergy was finally ruled out in 16 (31.4%) patients. Age, sex, atopy and family history of drug allergies were not significantly different between the patients with confirmed or ruled-out diagnosis of penicillin and amoxicillin allergy. CONCLUSION: At least up to one-third of patients with a history of beta-lactam allergy are proven to be safe using the drug. Also, a clear protocol consists of serum sIgE assay and SPT can be helpful to the physicians in the health care system.

Sildenafil in the treatment of pressure ulcer: a randomised clinical trial.

Pressure ulcer (PrU)-related hospitalisation and mortality are critical issues in medical and surgical patients. Although animal studies have suggested the beneficial effects of sildenafil on wound healing, related clinical data are lacking. This is the first clinical study that has evaluated the effects of topical sildenafil on PrU healing in human subjects. Enrolled patients were randomly allocated to receive topical sildenafil (10%) ointment or placebo daily. Wound healing was assessed visually and photographically by the change in wound score according to two-digit Stirling scale. Decreases in grades of the PrUs were significantly higher in sildenafil group compared with placebo group (P < 0·001). In addition, surface areas of ulcers in sildenafil group were significantly reduced compared to the control group at day 14 of intervention (P = 0·007). It appears that these effects may be mediated by improvement of microvascular reperfusion in the skin and soft tissue. Further study to emphasise the role of topical sildenafil in the prevention or treatment of PrUs in hospitalised patients is required.

Efficacy of topical atorvastatin for the treatment of pressure ulcers: a randomized clinical trial.

STUDY OBJECTIVE: To evaluate the effects of topical atorvastatin on the healing process of pressure ulcers in critically ill patients. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: Medical-surgical intensive care unit of a university-affiliated teaching hospital in Tehran, Iran. PATIENTS: One hundred four patients with stage I or II pressure ulcers, graded according to the 2-digit Stirling Pressure Sore Severity Scale. INTERVENTION: Patients were randomized to receive topical atorvastatin 1% ointment (51 patients [atorvastatin group]) or placebo ointment (53 patients [control group]) applied once/day to pressure ulcers for 14 days in addition to standard care for pressure ulcers. MEASUREMENTS AND MAIN RESULTS: The efficacy of each treatment was assessed on days 7 and 14. Efficacy was determined based on the degree of healing of the existing pressure ulcer by using the 2-digit Stirling scale. The baseline stage of the pressure ulcers did not differ significantly between the control and atorvastatin groups. However, the mean ± SD stage of pressure ulcers significantly decreased in the atorvastatin group compared with the control group on day 7 (0.97 ± 0.76 vs 1.74 ± 0.75, p<0.01) and day 14 (0.42 ± 0.67 vs 1.71 ± 0.78, p<0.01) of treatment. In addition, the mean ± SD surface areas of ulcers in the atorvastatin group were significantly declined compared with the control group after 7 days (5.55 ± 4.55 vs 9.41 ± 5.03 cm², p<0.01) and 14 days (3.72 ± 4.45 vs 10.41 ± 6.41 cm², p<0.01) of treatment. CONCLUSION: Topical application of atorvastatin ointment 1% for 14 days in addition to standard care significantly accelerated the healing of stage I or II pressure ulcers in critically ill patients.

Physicochemical and biological characterization of pep-1/elastin complexes.

Transdermal drug delivery of proteins is challenging because the skin acts as a natural and protective barrier. Several techniques including using the cell-penetrating peptides have been studied to increase the penetration of therapeutic proteins into and through the skin. Cell-penetrating peptides facilitate and improve the transduction of large and hydrophilic cargo molecules through plasma membrane. We have recently reported an efficient skin delivery of elastin protein in complex with a cell-penetrating peptide called Pep-1. As the biophysical characteristics of cell-penetrating peptide/protein complexes have been linked with their biological responses, in this study, we investigated biophysical properties of Pep-1/elastin complexes (ratio 10:1) stored in three temperatures (-20 °C, 4 °C and 25 °C) by photon correlation spectroscopy, circular dichroism and isothermal denaturation. We also evaluated the ability of transduction of this complex into cells and skin tissue using both fluorescence microscopy and Kodak In-Vivo FX Pro Imaging System.

Cell-penetrating peptides as a novel transdermal drug delivery system.

In the last decade, almost one-third of the newly discovered drugs approved by the US FDA were biomolecules and biologics. Effective delivery of therapeutic biomolecules to their target is a challenging issue. Innovations in drug delivery systems have improved the efficiency of many of new biopharmaceuticals. Designing of novel transdermal delivery systems has been one of the most important pharmaceutical innovations, which offers a number of advantages. The cell-penetrating peptides have been increasingly used to mediate delivery of bimolecular cargoes such as small molecules, small interfering RNA nucleotides, drug-loaded nanoparticles, proteins, and peptides, both in vitro and in vivo, without using any receptors and without causing any significant membrane damage. Among several different drug delivery routes, application of cell-penetrating peptides in the topical and transdermal delivery systems has recently garnered tremendous attention in both cosmeceutical and pharmaceutical research and industries. In this review, we discuss history of cell-penetrating peptides, cell-penetrating peptide/cargo complex formation, and their mechanisms of cell and skin transduction.

A peptide carrier for the delivery of elastin into fibroblast cells.

BACKGROUND: Transmembrane delivery of active peptides and proteins, including skin delivery of cosmeceutical proteins such as collagen and elastin, has been a challenging issue. Amphipathic cell-penetrating peptides (CPPs) have been proposed as carrier peptides to mediate cellular uptake of proteins without covalent binding. MATERIALS AND METHODS: In this study, we have used a short peptide, Pep-1, as our CPP to transport elastin into fibroblast cells. Different ratios of Pep-1/elastin complexes were produced by using a fixed amount of elastin and different molar ratio of Pep-1. The ability of transduction into cells was determined by fluorescence microscopy. The characteristics of Pep-1/elastin complexes were monitored using scanning electron microscopy and photon correlation spectroscopy. RESULTS: No cellular toxicity was observed in cells treated with Pep-1/elastin complex. Finally, we determined a Pep-1 : elastin ratio of 10 : 1 as the most effective ratio in cellular delivery of elastin. CONCLUSION: Pep-1 mediated fast and effective delivery of elastin as a cosmetic protein into fibroblast cells in the treatment of skin-aging symptoms.

Potential role of statins on wound healing: review of the literature.

Wound healing is a dynamic and complex biological process, which requires coordinated events including haemostasis, inflammation, proliferation, revascularisation and remodelling. Impaired wound healing is a common problem that occurs in both community and hospital settings. Various experimental and clinical studies have evaluated different modalities for the treatment of topical wounds, such as sugar, antibiotics, honey and phytotherapies; also statins have diverse pleiotropic effects that have been suggested to be useful to improve wound healing. Data derived from both animal and human studies showed that statins especially atorvastatin, simvastatin and pravastatin can accelerate the wound-healing process. However, further high-quality and evidence-based studies are needed to address the best statin drug, appropriate dose, the best administration route, duration of treatment and to determine correlation between pleiotropic effects of statins and their probable clinical benefits.

Novel formulation and evaluation of a Q10-loaded solid lipid nanoparticle cream: in vitro and in vivo studies.

Solid lipid nanoparticles (SLNs) of coenzyme Q10 (CoQ10) were formulated by a high-pressure homogenization method. The best formulation of SLN dispersion consisted of 13% lipid (cetyl palmitate or stearic acid), 8% surfactant (Tween 80 or Tego Care 450), and water. Stability tests, particle size analysis, differential scanning calorimetry, transmission electron microscopy, and release study were conducted to find the best formulation. A simple cream of CoQ10 and a cream containing CoQ10-loaded SLNs were prepared and compared on volunteers aged 20-30 years. SLNs with particle size between 50 nm and100 nm exhibited the most suitable stability. In vitro release profiles of CoQ10 from simple cream, SLN alone, and CoQ10-loaded SLN cream showed prolonged release for SLNs compared with the simple cream, whereas there was no significant difference between SLN alone and SLN in cream. In vitro release studies also demonstrated that CoQ10-loaded SLN and SLN cream possessed a biphasic release pattern in comparison with simple cream. In vivo skin hydration and elasticity studies on 25 volunteers suggested good dermal penetration and useful activity of Q10 on skin as a hydratant and antiwrinkle cream.

Topical delivery of urea encapsulated in biodegradable PLGA microparticles: O/W and W/O creams.

This study describes the formulation and characterization of O/W and W/O creams containing urea-loaded microparticles prepared with poly (D, L-lactic-co-glycolic acid) (PLGA) in order to encapsulate and stabilize urea. The solvent evaporation method was used for preparing PLGA microparticles containing urea. The microparticles size was evaluated by laser light diffractometry. The resulting microparticles were then incorporated in O/W and W/O creams and stability and the release pattern from the creams was evaluated by UV-spectrophotometry. The particle size of PLGA microparticles was in the range of 1-5 microm and most microparticles had a particle size smaller than 3 microm. The encapsulation efficiency was calculated as 40.5% +/- 3.4. This study also examined release pattern of urea which varied among different formulations. The results showed that the release from O/W creams followed Higuchi kinetics while the release from W/O creams showed the zero order kinetics and the creams containing microparticulated urea had slower release than free urea creams.

Preparation and characterization of biodegradable urea-loaded microparticles as an approach for transdermal delivery.

This work describes the formulation and characterization of urea-loaded microspheres prepared using various polymers such as ethyl cellulose (EC), cellulose acetate phthalate (CAP) and poly (D,L-lactic-co-glycolic acid) (PLGA), along with the utilization of a solvent evaporation technique. The effect of various formulation parameters (i.e. polymer type and concentration, vehicle type, polymer solution/vehicle volume ratio, drug/polymer ratio, homogenizer and stirrer speed, sonication time and speed, type of washing solution, drying and separation method) on the characteristics of microspheres was also evaluated. Results obtained indicated that, in the presence of urea, highest rate of EC microsphere production could be obtained at a drug/polymer ratio of 1:2 and a polymer solution/vehicle volume ratio of 1:50. In some cases, crystallization of urea was observed during the encapsulation process using cellulose derivative polymers. CAP microparticles showed a rough and tortuous surface while EC microparticles had a wider range of particle size. However, with the PLGA polymer, much better desired microparticles with a smaller size range of 1-3 microm were obtained. In general, PLGA microspheres were spherical in shape and possessed smooth surfaces with less pores in comparison with those obtained by the other polymers. The yield of particle production and the extent of urea encapsulation in PLGA particles were measured to be 68.87% +/- 5.3 and 40.5% +/- 3.4, respectively. The release study from PLGA microspheres revealed that up to 70% of the drug was released within a few days, through a four-stage release pattern.

Preparation of gelatin microspheres containing lactic acid--effect of cross-linking on drug release.

In this study, gelatin microspheres containing lactic acid were prepared by the polymerization technique using glutaraldehyde as the cross-linking agent. Dried microspheres were loaded by immersing them in an aqueous solution of lactic acid. In order to prepare microspheres with an appropriate drug release profile, the effect of time of cross-linking and the amount of cross-linking agent on the swelling properties of microspheres and their release profile were investigated. The microencapsulation efficiency, microspheres appearance, particle size, swelling ratio and drug release profile were also studied. Microspheres prepared with a larger amount of cross-linking agent, or after longer cross-linking time, showed a reduced swelling ratio in aqueous media. In vitro release pattern of lactic acid from gelatin microspheres showed a biphasic profile and the release rates were reduced upon increasing the amount of cross-liking agent and prolonging the cross-linking time.